The non-invasive evaluation of liver involvement in patients with cystic fibrosis: A prospective study.

BACKGROUND AND AIMS: Porto-sinusoidal vascular disease (PSVD) has been described as the prominent pathology in liver explants of patients with cystic fibrosis (CF), but data outside the transplant setting are lacking. We aimed to investigate the prevalence of portal hypertension (PH) in CF-associated liver disease (CFLD) and develop an algorithm to classify liver involvement in CF patients. METHODS: This is a cross-sectional study of consecutive paediatric and adult patients in a tertiary centre between 2018 and 2019, who underwent ultrasound, liver (LSM) and spleen stiffness (SSM) measurement. CFLD was defined according to physical examination, liver tests and ultrasound findings. PSVD was likely if there were PH signs in the absence of advanced chronic liver disease (CF-ACLD, LSM <10 kPa). A historical cohort was used to validate the prognostic significance of the new definitions. RESULTS: Fifty (27.5%) patients met CFLD criteria. At least one sign of PH was found in 47 (26%) patients, but most (81%) had LSM <10 kPa and were likely to have PSVD; only 9 (5%) had CF-ACLD. PSVD and CFLD (LSM <10 kPa) co-existed in most (23/36) cases. In the historical cohort (n = 599 patients), likely PSVD and CFLD+PH were independently associated with a 2-fold and 3.5-fold increase in mortality compared to patients without PH, respectively. In 34 patients with SSM, values <21 and >50 kPa accurately diagnosed specific signs of PH. CONCLUSIONS: PSVD is the prevailing cause of PH in CF patients. We developed a new diagnostic algorithm based on clinical and elastosonography criteria to classify liver involvement in patients with CF.

Sarcopenia Predicts Major Complications after Resection for Primary Hepatocellular Carcinoma in Compensated Cirrhosis.

The burden of post-operative complications of patients undergoing liver resection for hepatocellular carcinoma (HCC) is a cause of morbidity and mortality. Recently, sarcopenia has been reported to influence the outcome of patients with cirrhosis. We aimed to assess factors associated with sarcopenia and its prognostic role in liver surgery candidates. We included all patients with compensated advanced chronic liver disease (cACLD) undergoing liver resection for primary HCC consecutively referred to the University of Bologna from 2014 to 2019 with an available preoperative abdominal CT-scan performed within the previous three months. A total of 159 patients were included. The median age was 68 years, and 80.5% of the patients were male. Sarcopenia was present in 82 patients (51.6%). Age and body mass index (BMI) were associated with the presence of sarcopenia at multivariate analysis. Thirteen (8.2%) patients developed major complications and 14 (8.9%) presented PHLF grade B-C. The model for end-stage liver disease score was associated with the development of major complications, whereas cACLD presence, thrombocytopenia, portal hypertension (PH), Child-Pugh score and Albumin-Bilirubin score were found to be predictors of clinically significative PHLF. The rate of major complications was 11.8% in sarcopenic patients with cACLD compared with no complications (0%) in patients without sarcopenia and cACLD (p = 0.032). The rate of major complications was significantly higher in patients with (16.3%) vs. patients without (0%) sarcopenia (p = 0.012) in patients with PH. In conclusion, sarcopenia, which is associated with age and BMI, may improve the risk stratification of post-hepatectomy major complications in patients with cACLD and PH.

Assessment of liver stiffness measurement and ultrasound findings change during inotuzumab ozogamicin cycles for relapsed or refractory acute lymphoblastic leukemia.

In adult patients, acute lymphoblastic leukemia (ALL) is a rare hematological cancer with a cure rate below 50% and frequent relapses. With traditional therapies, patients with relapsed or refractory (R/R) ALL have a survival that may be measured in months; in these patients, inotuzumab ozogamicin (IO) is an effective therapy. IO was linked to increased risk of veno-occlusive disease/sinusoid obstruction syndrome (VOD/SOS), liver injury, and various grade of liver-related complications during clinical trials and real-life settings; however, hepatologic monitoring protocol is not established in this population. In our institution, 21 patients who received IO (median of 6 doses of IO administered) for R/R ALL were prospectively followed for hepatologic surveillance, including clinical evaluation, ultrasonography, and liver stiffness measurement (LSM) biochemistry. After a median follow-up of 17.2 months, two SOS events were reported (both after allogeneic transplant) as IO potentially related clinically relevant adverse event. Mild alterations were reported in almost the totality of patients and moderate-severe liver biochemical alterations in a quarter of patients. Within biochemicals value, AST and ALP showed an augment related to IO administration. LSM linearly augmented for each IO course administered. Baseline LSM was related to liver-related changes, especially with the severity of portal hypertension (PH)-related complications. Pre-transplant LSM was higher in patients receiving IO when compared with a control cohort. PH-related complications were discovered in nearly 77% of patients, with clinically significant PH occurrence and development of ascites in 38% and 14%, respectively. This prospective experience constitutes the rationale to design a hepatologic monitoring program in patients receiving IO. LSM may be of pivotal importance in this program, constituting a rapid and effective screening that quantitatively correlates with liver alterations.

Validation of a standardized CT protocol for the evaluation of varices and porto-systemic shunts in cirrhotic patients.

PURPOSE: The aim of the present study was to propose and validate a standardized CT protocol for evaluating all the types of portosystemic collaterals (P-SC), including gastroesophageal varices and spontaneous portosystemic shunts (SPSS), and to evaluate the prognostic role of portal hypertension CT features for the prediction of the hepatic decompensation risk in cirrhotic patients. METHODS: A retrospective cohort study of 184 advanced chronic liver disease who underwent CT scan between January 2014 and December 2017. Patients with an interval > 6 months between the imaging, elastometric, endoscopic and biochemical evaluation were excluded, as well as patients with previous transjugular intrahepatic portosystemic shunt (TIPS), liver transplantation (LT) or terminal medical conditions. Data on liver disease history, co-morbidities, endoscopic and radiologic findings were collected. The incidence of hepatic decompensation and other events, such as portal vein thrombosis, HCC, TIPS placement, LT, death, and its cause, were also recorded. The procedure was performed at baseline and after the administration of contrast agent using a multiphasic technique and bolus tracking. Two senior radiologists working in different centres and a non-expert radiologist reviewed all CT examinations, to evaluate both intra-observer and inter-observer variability of the CT protocol and to obtain an external validation. The radiological variables were evaluated using both univariate and adjusted multivariate competing risk regression models. RESULTS: Both intra-observer and inter-observer agreement were excellent in detection and measurement of almost all types of P-SC. The presence of SPSS, a spleen diameter > 16 cm, a portal vein diameter > 17 mm and the presence of ascites resulted independent predictors of decompensation-free survival for cirrhotic patients and were incorporated in an easy-to-use score (AUROC = 0.799, p-value = 0.732) which can the risk of decompensation at 5 years, ranking it as low (11.3%), moderate (35.6%) or high (70.8%). CONCLUSIONS: The CT protocol commonly performed during the HCC surveillance program for cirrhotic patients is valid for detecting all types of P-SC. The radiological score identified to predict the decompensation-free survival for cirrhotic patients could be an easy-to-use clinical tool.

Clinical Presentation of Celiac Disease and Diagnosis Accuracy in a Single-Center European Pediatric Cohort over 10 Years.

(1) Background: Changes in the clinical presentation of celiac disease (CD) in children have been reported. The guidelines of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) allow esophagogastroduodenoscopy (EGD) with biopsies to be avoided under specific circumstances. We aimed to assess the clinical picture of pediatric CD patients at diagnosis and to validate ESPGHAN non-biopsy criteria. (2) Methods: Patients with suspected CD or undergoing screening from 2004 to 2014 at the University Hospital in Modena, Italy were enrolled. The accuracy of ESPGHAN non-biopsy criteria and modified versions were assessed. (3) Results: In total, 410 patients were enrolled, of whom 403 were considered for analysis. Of the patients considered, 45 were asymptomatic and diagnosed with CD (11.2%) while 358 patients (88.2%) were symptomatic, of whom 295 were diagnosed with CD. Among symptomatic CD patients, 57 (19.3%) had gastrointestinal symptoms, 98 (33%) had atypical symptoms and 140 (47.4%) had both. No difference was found for the presence of gastrointestinal symptoms at different ages. The non-biopsy ESPGHAN criteria yielded an accuracy of 59.4% with a positive predictive value (PPV) of 100%; 173 out of 308 EGD (56.2%) could have been avoided. The modified 7× and 5× upper limit of normal cut-offs for IgA anti tissue-transglutaminase reached 60.7% and 64.3% of EGD avoided, respectively. (4) Conclusions: Over 10 years, late age at diagnosis and increased rates of atypical CD presentation were found. ESPGHAN non-biopsy criteria are accurate for CD diagnosis and allow half of unneeded EGD to be avoided. Modified versions allowed sparing a greater number of EGD.

A Nomogram-Based Prognostic Model for Advanced Hepatocellular Carcinoma Patients Treated with Sorafenib: A Multicenter Study.

Among scores and staging systems used for HCC, none showed a good prognostic ability in patients with advanced HCC treated with Sorafenib. We aimed to evaluate predictive factors of overall survival (OS) and drug response in HCC patients undergoing Sorafenib included in the Italian Liver Cancer (ITA.LI.CA.) multicenter cohort. Patients in the ITA.LI.CA database treated with Sorafenib and updated on 30 June 2019 were included. Demographic and clinical data before starting Sorafenib treatment were considered. For the evaluation of predictive factors for OS, a time-dependent Cox proportional hazard model was used. A total of 1107 patients were included in our analysis. The mean age was 64.3 years and 81.7% were male. Most patients were staged as BCLC B (205, 18.9%) or C (706, 65.1%). The median time of Sorafenib administration was 4 months (interquartile range (IQR) 2-12), and the median OS was 10 months (IQR: 4-20). A total of 263 patients (33.8%) out of 780 with available evaluation experienced objective tumoral response to Sorafenib. The Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) (hazard ratio (HR) 1.284), maximum tumoral diameter (HR 1.100), plasma total bilirubin (HR 1.119), aspartate amino transferase assessed as multiple of the upper normal value (HR 1.032), alpha-fetoprotein ≥200 ng/mL (HR 1.342), hemoglobin (HR 0.903) and platelet count (HR 1.002) were associated with OS at multivariate Cox regression analysis. Drug response was predicted by maximum tumoral diameter and platelet count. A novel prognostic nomogram for patients undergoing Sorafenib is hereby proposed. The novelty introduced is the comprehensive patient's assessment using common markers of patient's general status, liver damage and function and HCC biology. Further studies are required to test its accuracy and provide external validation.

Prognostic Value of the Albumin-Bilirubin Grade for the Prediction of Post-Hepatectomy Liver Failure: A Systematic Review and Meta-Analysis.

(1) Introduction: Liver resection (LR) for hepatocellular carcinoma (HCC) is often burdened by life-threatening complications, such as post-hepatectomy liver failure (PHLF). The albumin-bilirubin (ALBI) score can accurately evaluate liver function and the long-term prognosis of HCC patients, including PHLF. We aimed to evaluate the diagnostic value of the ALBI grade in predicting PHLF in HCC patients undergoing LR. (2) Methods: MEDLINE, Embase, and Scopus were searched through January 17th, 2021. Studies reporting the ALBI grade and PHLF occurrence in HCC patients undergoing LR were included. The Odds Ratio (OR) prevalence with 95% confidence intervals (CI) was pooled, and the heterogeneity was expressed as I2. The quality of the studies was assessed using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies). (3) Results: Seven studies met the inclusion criteria and were included in the analysis. A total of 5377 patients who underwent LR for HCC were considered, of whom 718 (13.4%) developed PHLF. Patients with ALBI grades 2 and 3 before LR showed increased rates of PHLF compared to ALBI grade 1 patients. The pooled OR was 2.572 (95% CI, 1.825 to 3.626, p < 0.001), with substantial heterogeneity between the studies (I2 = 69.6%) and no publication bias (Begg's p = 0.764 and Egger's p = 0.851 tests). All studies were at a 'low risk' or 'unclear risk' of bias. Univariate meta-regression analysis showed that heterogeneity was not dependent on the country of study, the age and sex of the participants, the definition of PHLF used, the rate of patients in Child-Pugh class A or undergoing major hepatectomy. (4) Conclusions: In this meta-analysis of published studies, individuals with ALBI grades of 2 and 3 showed increased rates of PHLF compared to ALBI grade 1 patients.

Risk of hepatocellular carcinoma after HCV eradication: Determining the role of portal hypertension by measuring spleen stiffness.

BACKGROUND & AIMS: Hepatitis C virus (HCV) eradication with direct-acting antivirals (DAAs) reduces but does not eliminate the risk for hepatocellular carcinoma (HCC). The development of surveillance strategies for HCC after the sustained virologic response (SVR) is therefore warranted. We aimed to evaluate the role of spleen stiffness measurement (SSM) in the prediction of HCC risk in a cohort of patients with advanced chronic liver disease (ACLD) treated with DAAs. METHODS: This is a retrospective cohort study of 140 patients with HCV-related ACLD successfully treated with DAAs in our centre between 2015 and 2017. Patients with available liver stiffness (LSM) and SSM before treatment and 6 months after (SVR24) were included. A Cox regression model investigated the association between SSM and HCC development. RESULTS: During a median follow-up of 41.5 (IQR 32-49) months, 20 patients presented with HCC. SSM at SVR24 predicted HCC development in univariate and adjusted multivariate analysis (hazard ratio: 1.025; 95% CI: 1.001-1.050); the best cut-off was 42 kPa. Patients with LSM-SVR24 ≤10 kPa were at the lowest risk of HCC. In patients with LSM-SVR24 >10 kPa, HCC incidence was not further influenced by LSM values (10-20 kPa vs. >20 kPa), but only by SSM-SVR24 values (≤42 vs. >42 kPa). CONCLUSIONS: Portal hypertension, as evaluated by SSM, plays a significant role in liver carcinogenesis after DAA treatment. We proposed a new algorithm based on post-treatment values of LSM and SSM for the stratification of HCC risk after SVR achievement. LAY SUMMARY: Spleen stiffness predicts the development of hepatocellular carcinoma after viral eradication, especially in patients with post-treatment liver stiffness values >10 kPa. An algorithm based on liver and spleen stiffness can stratify for the risk of liver cancer development and guide the surveillance strategies after treatment with direct-acting antivirals.

The role of liver and spleen elastography in advanced chronic liver disease.

Portal hypertension is the main driver of complications in patients with advanced chronic liver disease (ACLD). In the last decade, many non-invasive tests, such us liver and spleen elastography, have been proposed and validated for the identification of patients with clinically significant portal hypertension (CSPH) and its complications, mainly hepatic decompensation and liver-related morbidity and mortality. Moreover, elastography accurately stratifies for the risk of HCC development, HCC recurrence and decompensation after liver surgery. Recent studies suggest a role of SSM in monitoring response to treatments and interventions in ACLD, such as viral eradication, non-selective beta-blockers and transjugular intrahepatic portosystemic shunt placement. However, one of the most indications to perform elastography in ACLD still remains the screening for esophageal varices. In fact, according to the Baveno VI consensus, liver stiffness measurement (LSM) <20 kPa and platelet count >150,000/mm3 can safely identify patients at low risk of varices requiring treatment (VNT) and could therefore avoid invasive upper invasive endoscopy; LSM>20-25 kPa can accurately rule-in CSPH in patients with viral etiology. Spleen stiffness measurement (SSM) is a direct surrogate of portal hypertension and has been demonstrated more accurate in predicting portal hypertension severity and VNT. A combined model including Baveno VI Criteria and SSM (≤46 kPa) can significantly increase the number of spared endoscopies (>40-50%), maintaining a low (<5%) of missed VNT.

Comparison of prognostic models in advanced hepatocellular carcinoma patients undergoing Sorafenib: A multicenter study.

BACKGROUND: Sorafenib is the gold standard therapy for the advanced hepatocellular carcinoma (HCC). No scoring/staging is universally accepted to predict the survival of these patients. AIMS: To evaluate the accuracy of the available prognostic models for HCC to predict the survival of advanced HCC patients treated with Sorafenib included in the Italian Liver Cancer (ITA.LI.CA.) multicenter cohort. METHODS: The performance of several prognostic scores was assessed through a Cox regression-model evaluating the C-index and the Akaike Information Criterion (AIC). RESULTS: Data of 1129 patients were analyzed. The mean age of patients was 61.6 years, and 80.8% were male. During a median follow-up period of 13 months, 789 patients died. The median period of Sorafenib administration was 4 months. All the prognostic scores were able to predict the overall survival (p<0.001) at univariate analysis, except the Albumin-Bilirubin score. The Italian Liver Cancer score (CLIP) yielded the highest accuracy (C-index 0.604, AIC 9898), followed by the ITA.LI.CA. prognostic score (C-index 0.599, AIC 9915). CONCLUSIONS: The CLIP score had the highest accuracy in predicting the overall survival of HCC patients treated with Sorafenib, although its performance remained poor. Further studies are needed to refine the current ability to predict the outcome of HCC patients undergoing Sorafenib.

Is Ultrasound Elastography Useful in Predicting Clinically Relevant Pancreatic Fistula After Pancreatic Resection?: A Systematic Review and Meta-analysis.

OBJECTIVES: Ultrasound (US) elastography has been proposed for the non-invasive prediction of clinically relevant pancreatic fistula (CR-POPF) in patients undergoing pancreatic resection. We aimed to perform a systematic review with meta-analysis to assess the diagnostic value of US elastography in predicting CR-POPF. METHODS: MEDLINE via PubMed, Ovid Embase, Scopus, and Cochrane Library databases, and abstracts of international conference proceedings were searched up to April 20, 2020. Studies assessing the performance of abdominal US elastography in predicting CR-POPF in patients undergoing pancreatic resection were included. The quality of the studies was assessed using Quality Assessment of Diagnostic Accuracy Studies. RESULTS: Five studies, including 247 patients who underwent partial pancreatic resection of whom 72 patients experiencing CR-POPF, were selected. All studies performed US elastography in different pancreatic sites. The pooled mean strain value was lower in pancreatic segments of patients experiencing CR-POPF than in those without, with a pooled weighted mean difference of -0.187 (95% confidence intervals, -0.303 to -0.071; P = 0.002). There was low heterogeneity between studies (I = 7.6%), and all studies were at "high risk" or "unclear risk" of bias. CONCLUSIONS: This study provides evidence that US elastography values are statistically significantly lower in patients experiencing CR-POPF.

Clinical impact of sarcopenia assessment in patients with hepatocellular carcinoma undergoing treatments.

Changes in body composition are associated with poor outcomes in cancer patients including hepatocellular carcinoma (HCC). Sarcopenia, defined as the loss of skeletal muscle mass, quality and function, has been associated with a higher rate of complications and recurrences in patients with cirrhosis and HCC. The assessment of patient general status before HCC treatment, including the presence of sarcopenia, is a key-point for achieving therapy tolerability and to avoid short- and long-term complications leading to poor patients' survival. Thus, we aimed to review the current literature evaluating the role of sarcopenia assessment related to HCC treatments and to critically provide the clinicians with the most recent and valuable evidence. As a result, sarcopenia can be predictive of poor outcomes in patients undergoing liver resection, transplantation and systemic therapies, offering the chance to clinicians to improve the muscular status of these patients, especially those with high-grade sarcopenia at high risk of mortality. Further studies are needed to clarify the predictive value of sarcopenia in other HCC treatment settings and to evaluate its role as an additional staging tool for identifying the most appropriate treatment. Besides, interventional studies aiming at increasing the skeletal muscle mass for reducing complications and increasing the survival in patients with HCC are needed.

Non-invasive tests for the prediction of primary hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world and it is one of the main complications of cirrhosis and portal hypertension. Even in the presence of a well-established follow-up protocol for cirrhotic patients, to date poor data are available on predictive markers for primary HCC occurrence in the setting of compensated advanced chronic liver disease patients (cACLD). The gold standard method to evaluate the prognosis of patients with cACLD, beyond liver fibrosis assessed with histology, is the measurement of the hepatic venous pressure gradient (HVPG). An HVPG ≥10 mmHg has been related to an increased risk of HCC in cACLD patients. However, these methods are burdened by additional costs and risks for patients and are mostly available only in referral centers. In the last decade increasing research has focused on the evaluation of several, simple, non-invasive tests (NITs) as predictors of HCC development. We reviewed the currently available literature on biochemical and ultrasound-based scores developed for the non-invasive evaluation of liver fibrosis and portal hypertension in predicting primary HCC. We found that the most reliable methods to assess HCC risk were the liver stiffness measurement, the aspartate aminotransferase to platelet ratio index score and the fibrosis-4 index. Other promising NITs need further investigations and validation for different liver disease aetiologies.

Spleen stiffness measurement for assessing the response to ß-blockers therapy for high-risk esophageal varices patients.

BACKGROUND: Non-selective ß-blocker (NSBB) therapy is the treatment of choice for primary prophylaxis of cirrhotic patients with high-bleeding risk esophageal varices (HRV). The hemodynamic response to NSBB is assessed by the measurement of the hepatic venous pressure gradient (HVPG). Recently, liver and spleen stiffness measurements (LSM and SSM) were proposed as non-invasive surrogates of HVPG. We aimed to evaluate LSM and SSM changes for assessing hemodynamic response in these patients. METHODS: Cirrhotic patients with HRV were prospectively enrolled and evaluated at our Department before starting NSBB and after 3 months. Correlation between changes (delta) of HVPG after NSBB treatment and those of LSM or SSM by transient elastography was performed. RESULTS: From the initial 59 patients considered for the study, 20 were finally included in the analysis. Fifteen (15) patients reached hemodynamic response to NSBB according to HVPG. Changes in LSM did not correlate with changes in HVPG (r = 0.107, p value = 0.655), unlike changes in SSM (r = 0.784, p value < 0.0001). Delta SSM presented excellent accuracy in identifying HVPG responders (AUROC 0.973; 95% CI 0.912-1). The best cut-off for delta SSM to identify responders was -10% (sensitivity 100%, specificity 60%, NPV 100% and PPV 90%). CONCLUSIONS: SSM could be a reliable non-invasive test for the assessment of hemodynamic response to NSBB therapy as primary prophylaxis for HRV. Similar to HVPG, SSM reduction ≥ 10% is able to assess hemodynamic response.

A nomogram based on liver stiffness predicts postoperative complications in patients with hepatocellular carcinoma.

BACKGROUND & AIMS: Liver stiffness measurement (LSM), assessed by transient elastography (Fibroscan), has been demonstrated to predict post-hepatectomy liver failure in patients who undergo hepatic resection for hepatocellular carcinoma (HCC). However, other complications are also likely to be related to the underlying grade of liver fibrosis. Herein, we aimed to identify predictors of postoperative complications and to build and develop a novel nomogram able to identify patients at risk of developing severe complications. METHODS: Data from patients who underwent hepatectomy for HCC between 2006 and 2016 at 2 referral centres were retrospectively reviewed. All surgical complications were recorded and scored using the comprehensive complication index (CCI), ranging from 0 (uneventful course) to 100 (death). A CCI ≥26.2 was used as a threshold to define severe complications. RESULTS: During the study period, 471 patients underwent hepatic resection for HCC. Among them, 50 patients (10.6%) had a CCI ≥26.2. Age, model for end-stage liver disease (MELD) score and LSM values, together with serum albumin, were independent predictors of high CCI. The nomogram built on these variables was internally validated and showed good performance (optimism-corrected c-statistic = 0.751). A regression equation to predict the CCI was also established by multiple linear regression analysis: [LSM (kPa) × 0.254] + [age (years) × 0.118] + [MELD score (pt.) × 1.050] - [albumin (g/dl) × 2.395] - 3.639. CONCLUSION: A novel nomogram, combining LSM values, age and liver function tests provided an excellent preoperative prediction of high CCI in patients with resectable HCC. This predictive model could be used as a reference for clinicians and surgeons to help them in clinical decision-making. LAY SUMMARY: Liver stiffness measurement is increasingly being used to assess the degree of liver fibrosis in patients with cirrhosis and/or chronic hepatitis. Using Fibroscan, we developed a novel nomogram to predict severe complications following liver resection for hepatocellular carcinoma, according to the new comprehensive complication index. This tool could be used as a reference for clinicians and surgeons to help them in clinical decision-making.

Ablation for hepatocellular carcinoma: beyond the standard indications.

Hepatocellular carcinoma (HCC), the most common primary liver neoplasia, represents the fifth most common malignant disease in men. Percutaneous ablation treatment is recommended among the treatments suggested for HCC patients in the very early/early stage. In the last decade, very important results in terms of survival benefits have been obtained with local ablative therapies, also outside the standard indications, thanks to many technical innovations. In particular, important results of ablation as a safe and effective technique have been obtained in the treatment of intermediate- or advanced-stage patients with HCC, and in the treatment of unfavourable tumour locations. Moreover, awareness is growing regarding the necessity of overcoming the rigidity of traditional guidelines in the treatment of HCC due to the complexity of patients with HCC, focusing on Precision Medicine. In this context, it is important to know the standard and non-standard indications of ablation in the treatment of HCC in order to offer the best therapeutic option tailored for each patient. The aim of this study was to analyse the possible clinical applications of ablative therapies for HCC patients, beyond the traditional indications recommended in the most widespread clinical practice guidelines for the management of HCC.

Interleukin 28 Polymorphisms and Hepatocellular Carcinoma Development after Direct Acting Antiviral Therapy for Chronic Hepatitis C.

BACKGROUND AND AIMS: Cirrhotic patients with hepatitis C virus (HCV) infection remain at risk of developing hepatocellular carcinoma (HCC) even after the sustained virologic response (SVR). We aimed to evaluate whether the IL28 (rs12979860) single nucleotide polymorphism (SNP) may constitute a predisposing genetic factor and to identify the SVR patients at risk of HCC. METHODS: Two hundred patients undergoing DAAs treatment for chronic hepatitis C with advanced fibrosis (F3- F4) were consecutively enrolled. Besides normal routine laboratory testing for HCV, patients' sera were evaluated also for retinol, retinol-binding protein 4 and the following SNPs: PNPLA3 (rs738409), TM6SF2 (rs58542926), MBOAT7 (rs641738), IL28B (rs12979860), TIMP-1 (rs4898), TIMP-2 (rs8179090), NF-kB promoter (rs28362491). Statistical analyses were conducted using Stata/SE 14.2 statistical software (Stata Corp, College Station, TX). RESULTS: Almost all patients (197/200) obtained SVR24. Seventeen patients had a previous history of treated HCC before DAAs. Six patients developed HCC recurrence and five patients developed de novo HCC after a mean period of 18 months since EOT. All these patients had SVR. A significant association between IL28B - TT genotype and HCC development after DAAs therapy was observed (OR 4.728, CI 95% 1.222 - 18.297, p=0.024). CONCLUSION: IL28B rs12979860 polymorphism was significantly associated with HCC development after DAAs. Assessment of this SNP may better identify patients at risk of developing HCC after treatment. Further prospective studies are required to confirm these hypotheses.

Longitudinal evaluation of liver stiffness in three pediatric patients with veno-occlusive disease.

Liver stiffness measurement by transient elastography is a non-invasive ultrasound-based technique used mainly for the evaluation of liver fibrosis in patients with chronic liver diseases. Some authors have suggested that it could be useful in the assessment of hepatic complications during hematopoietic stem cell transplant (HSCT), especially veno-occlusive disease (VOD) or sinusoidal obstructive syndrome (SOS). Here, we present the evaluation of liver stiffness in three patients who developed severe hepatic VOD/SOS after HSCT. Liver stiffness measurement values were normal before transplant and afterward until the diagnosis of VOD/SOS when a dramatic increase was observed. After the VOD/SOS specific treatment, the values of stiffness showed a similar pattern of progressive reduction in all the three patients, with normalization after two weeks. In this report, we discuss the role of LSM in the management of patients after the diagnosis of VOD/SOS.

Nerve fiber overgrowth in patients with symptomatic diverticular disease.

BACKGROUND: Colonic diverticulosis is a common condition in industrialized countries. Up to 25% of patients with diverticula develop symptoms, a condition termed symptomatic uncomplicated diverticular disease (SUDD). The aim of the present study was to characterize neuroimmune interactions and nerve fiber plasticity in the colonic mucosa of patients with diverticula. METHODS: Controls, patients with diverticulosis and with SUDD were enrolled in the study. Mucosal biopsies were obtained close to diverticula (diverticular region) and in a normal mucosa (distant site), corresponding to sigmoid and descending colon in the controls. Quantitative immunohistochemistry was used to assess mast cells, T cells, macrophages, nerve fibers, and neuronal outgrowth (growth-associated protein 43, GAP43+fibers). KEY RESULTS: No difference emerged in mast cells and T cells among the three groups. Macrophages were increased in patients with SUDD and diverticulosis as compared to controls. Nerve fibers were enhanced in patients with SUDD and diverticulosis in comparison with controls in the diverticular region. GAP43+ fibers were increased only in patients with SUDD as compared to controls and to patients with diverticulosis in the diverticular region. In patients with SUDD, GAP43 density was increased in the diverticular region compared to distant site. Macrophages close to GAP43+ fibers were increased in the diverticular region of patients with SUDD. Significant correlations were found between GAP43+ fibers and immune cells. CONCLUSIONS AND INFERENCES: Patients with diverticula are characterized by increased macrophage counts, while nerve fiber sprouting is increased only in the diverticular region of patients with SUDD suggesting a role in symptom generation.